rs148912524

chr8-144515323-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_004260.4(RECQL4):c.1390+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,612,376 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0034 (18 hom.)
• Consequence: RECQL4 NM_004260.4 splice_donor_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.371

Genes affected

RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 8-144515323-C-T is Benign according to our data. Variant chr8-144515323-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 239696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144515323-C-T is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4	c.1390+3G>A		splice_donor_region_variant, intron_variant		ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6	c.1390+3G>A		splice_donor_region_variant, intron_variant		1	NM_004260.4	P1
RECQL4	ENST00000621189.4	c.319+3G>A		splice_donor_region_variant, intron_variant		1
RECQL4	ENST00000532846.2	c.275+3G>A		splice_donor_region_variant, intron_variant		5
RECQL4	ENST00000688394.1	n.413+3G>A		splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00242 AC: 368 AN: 152248 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00417

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00237 AC: 585 AN: 246886 Hom.: 5 AF XY: 0.00249 AC XY: 335 AN XY: 134482

Gnomad AFR exome AF: 0.000590

Gnomad AMR exome AF: 0.000872

Gnomad ASJ exome AF: 0.00141

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00213

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.00383

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00338 AC: 4928 AN: 1460010 Hom.: 18 Cov.: 33 AF XY: 0.00338 AC XY: 2458 AN XY: 726222

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000963

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00179

Gnomad4 FIN exome AF: 0.00159

Gnomad4 NFE exome AF: 0.00402

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.00241 AC: 367 AN: 152366 Hom.: 0 Cov.: 34 AF XY: 0.00242 AC XY: 180 AN XY: 74510

Gnomad4 AFR AF: 0.000769

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00416

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00354 Hom.: 1

Bravo AF: 0.00212

EpiCase AF: 0.00453

EpiControl AF: 0.00350

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:7

Likely benign, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2019	This variant is associated with the following publications: (PMID: 29220673) -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	RECQL4: BP4, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 31, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 16, 2021	- -

Rothmund-Thomson syndrome type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Hereditary cancer-predisposing syndrome Benign:1

Likely benign, criteria provided, single submitter

curation

Sema4, Sema4

Dec 27, 2020

- -

Baller-Gerold syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	7.6
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs148912524; hg19: chr8-145740707; COSMIC: COSV104618504; COSMIC: COSV104618504;